i. To compare the efficacy of (i) intermittent vismodegib vs. (ii) the efficacy of photodynamic therapy (PDT) in preventing the return of the burden of surgically eligible BCCs (SEBs) to baseline level following 7 months of continuous vismodegib therapy.

ii. To compare the cumulative diameter (burden) of SEBs in patients treated intermittently with vismodegib vs. with photodynamic therapy (PDT).

Vismodegib is a small molecule inhibitor of SMO developed by Genentech for treatment of tumors in which the HH signaling pathway appears to contribute to development and maintenance of tumorigenesis. Vismodegib, a systemic HH pathway antagonist, has been shown to have oral bioavailability and potent anti-tumor activity in a variety of primary human tumor xenografts and tumor cell line xenograft models (see the Vismodegib Investigator Brochure).

Drug: GDC-0449

150 mg per day for 7 continuous months then randomized for 3 month intervals to 28 months.

Other Name: Erivedge

Experimental: Photodyanmic Therapy

Levulan(aminolevulinic acid HCl) is a drug that has come into prominence over the last two decades for its potential use in photodynamic therapy (PDT) of superficial, benign and malignant skin disorders. Aminolevulinic acid (ALA) is the natural precursor of protoporphyrin IX (PpIX) in the biosynthetic pathway leading to heme; it has been estimated that at least 358 mg ALA per day are synthesized by the human body to support endogenous heme production.

A New Drug Application (NDA) for treatment of non-hyperkeratotic actinic keratoses of the face or scalp with Levulan Kerastick for Topical Solution, 20% and 10 J/cm2 of visible (417 nm) blue light, was approved by the United States Food and Drug Administration (FDA) on December 03, 1999.

This is a Phase II, 28 month, randomized, two arm multicenter clinical study design. During the initial 7 months of the study, all 24 subjects will receive vismodegib, 150mg/day. They then will be randomized in a 1:1 ratio to receive intermittent vismodegib, 150 mg/day, during months 10-13, 16-19, and 22-25 or to receive treatment with PDT at month 10 and at three month intervals thereafter. The safety and efficacy of intermittent vismodegib and of PDT will be assessed at the time of the subjects' visits to the Study Center and at the time of telephone contacts. A Data Safety Monitoring Board (DSMB) will review results for an interim analysis when 12 subjects have completed 28 months. The DSMB review will focus on adverse events and efficacy results. Subjects will be monitored for the presence of surrogate endpoint biomarkers (SEBs) at each Study visit.

Eligibility

Ages Eligible for Study:

18 Years to 75 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

The subject:

has had diagnosed at least 10 SEB (of diameter 3 mm diameter or greater on the nose or periorbital skin, 5 mm or greater elsewhere on the face, or 9 mm or greater on non-facial areas excluding the skin below the knees) during the two years before study entry, as documented histologically in physicians' records and/or diagnosed clinically by a Study Investigator at baseline.

meet diagnostic criteria for basal cell nevus syndrome

is willing to abstain from application of non-study topical medications to the skin for the duration of the study, including prescription and over the counter preparations. For example, topical preparations containing corticosteroids (other than Triamcinolone applied no more than 6x/month) or vitamin A derivatives are not allowed. Moisturizers and emollients are allowable. Subjects will be encouraged to use sunscreen (SPF 15) at least once daily on all exposed skin sites.

is willing to forego treatment of BCCs unless the BCCs are documented by Study Investigators, preferably on two separate visits, except when the PSCP believes that delay in treatment potentially might compromise the health of the subject.

has normal laboratory tests as defined by the following: Normal hematopoietic capacity, Normal hepatic function: AST and ALT greater than or equal to 2x the upper limit of normal (ULN) Total bilirubin within normal range 0.20 mg/dl to 1.50 mg/dl or within 3x ULN for patients with Gilbert's disease Normal renal function: normal serum creatinine or measured creatinine clearance less than 50 mL/minute. Fasting cholesterol greater than or equal to 220 untreated

be willing to not donate blood or semen for three months following discontinuation of Study medications.

is willing to avoid pregnancy in his partner as defined by the following: Male subject is willing to use a latex condom during the study and for 3 months after the last dose during sexual contact with a female of childbearing potential, even if he has had a successful vasectomy. His partner must also use a form of birth control

Exclusion Criteria:

The subject:

has used topical or systemic therapies that might interfere with the evaluation of the study medication during the study. Specifically these include the use of: (i) glucocorticoids (other than Triamcinolone on no more than 36 days during the six months prior to study entry) to more than 5% of the skin (ii) retinoids (e.g., etretinate, isotretinoin, tazarotene, tretinoin, adapalene) systemically or topically to more than 5% of the skin during the six months prior to study entry; (iii) alpha-hydroxy acids (e.g., glycolic acid, lactic acid) to more than 5% of the skin during the six months prior to study entry (iv) 5-fluorouracil or imiquimod (except as topical treatment to discrete BCCs) systemically or topically to the skin above the knees during the six months prior to study entry. (v) treatment with systemic chemotherapy within one year prior to starting study medication.

has a history of hypersensitivity to any of the ingredients in the study medication formulations.

is unable to return for follow-up visits and tests.

has uncontrolled systemic disease, including known HIV positive patients.

has history of congestive heart failure.

has uncontrolled hypocalcemia, hypomagnesemia, or hypokalemia

has clinically important history of liver disease, including viral or hepatitis, current alcohol abuse, or cirrhosis.

has any condition or situation which in the Investigator's opinion may put the subject at significant risk, could confound the study results, or could interfere significantly with the subject's participation in the study. This includes history of other skin conditions or disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications

has a history of invasive cancer within the past five years excluding non-melanoma skin cancer, Stage I cervical cancer, ductal carcinoma in situ of the breast, or CLL Stage 0.

has current, recent (within 4 weeks of Day 1), or planned participation in an experimental drug study while enrolled in this study.

is a female who is pregnant, plans to ever to become pregnant, capable of becoming pregnant or is breast feeding.

is a male who is unwilling or unable to comply with pregnancy prevention measures.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556009